The National Cancer Institute estimates that about ten million Americans have or have had some form of cancer. Overall costs of the disease are $126 billion annually. According to the American Cancer Institute, prostate cancer is the second leading cause of cancer death in men in the United States.
Data from the National Institute of Cancer indicates that the current Prostate-specific antigen (PSA) test can fail to detect prostate cancer in some patients and lead to unnecessary biopsies for many others. Only 25-30% of men who have a biopsy due to elevated PSA levels actually have prostate cancer.
A more accurate test is desired to substantiate the diagnosis of prostatic adenocarcinoma and exclude mimicking conditions including atrophy, atypical adenomatous hyperplasia (AAH), nephrogenic adenoma and mesonephric hyperplasia. Current immunohistochemical diagnosis of prostate cancer depends on markers because no absolutely specific and sensitive marker for prostate cancer has been discovered. Even after current immunohistochemical diagnosis, the diagnosis of minimal prostatic adenocarcinoma can be ambiguous in prostate needle biopsy tissues.
Hexim-1 is a regulatory component of the positive elongation pTEFb complex and interacts with Cyclin T1, the partner of cyclin dependent kinase 9 (Cdk9), a serine kinase. The structure and further description of Hexim-1 is described by Dames et al. (2007), Proc. Natl. Acad. Sci USA 104:14312-7. Gene transcription by RNA polymerase II (RNA Pol II) proceeds by the steps of (a) initiation of RNA transcription, (b) elongation of the RNA transcript, and (c) termination of the RNA transcript. Each stage is highly regulated and requires the participation of multiple factors. When Hexim-1 is complexed within the pTEFb complex, the Cdk9 serine kinase is inactive. However, when Hexim-1 is released from the pTEFb complex, Cdk9 within the pTEFb complex can phosphorylate the serine residues of the carboxyl terminus domain (CTD) of RNA Pol II within the consensus site Tyr-Ser-Pro-Thr-Ser-Pro-Ser (SEQ ID NO: 6). Following phosphorylation of the CTD, RNA Pol II enters into the elongation phase. Thus, in the presence of Hexim-1 in the pTEFb complex, transcription does not proceed, while in the absence of Hexim-1, Cdk9 phosphorylates the CTD of RNA Pol II and transcription elongation occurs.